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Human monoclonal anti-D-induced clearance of human D-positive red cells in a chimpanzee model
A Blancher1, W W Socha, F Roubinet
1Laboratoire d'Anthropologie Physique du Collège de France, Paris.
Two human monoclonal anti-Rh0(D) antibodies, one IgG1, and one IgG3, were tested for their ability to clear human D-positive red blood cells (RBCs) from chimpanzee circulation. Human RBCs (phenotype A1, R1r) from 1 donor were radiolabelled with chromium 51 and injected into 4 chimpanzees. One day later the control animal received isotonic saline whereas 2 animals received 400 micrograms of purified human monoclonal anti-D, either IgG1 or IgG3. The remaining animal received both antibodies together (200 micrograms of IgG1 and 200 micrograms of IgG3). Both individual antibody-mediated clearance of human D-positive cells and synergy was not observed when both antibodies were used in combination. IgG1 was slightly more effective than IgG3. This animal model is a suitable alternative for conducting in vivo experiments in human beings, especially at the preclinical study phase of monoclonal anti-D antibodies.
Two human monoclonal anti-Rh0(D) antibodies, one IgG1, and one IgG3, were tested for their ability to clear human D-positive red blood cells (RBCs) from chimpanzee circulation. Human RBCs (phenotype A1, R1r) from 1 donor were radiolabelled with chromium 51 and injected into 4 chimpanzees. One day later the control animal received isotonic saline whereas 2 animals received 400 micrograms of purified human monoclonal anti-D, either IgG1 or IgG3. The remaining animal received both antibodies together (200 micrograms of IgG1 and 200 micrograms of IgG3). Both individual antibody-mediated clearance of human D-positive cells and synergy was not observed when both antibodies were used in combination. IgG1 was slightly more effective than IgG3. This animal model is a suitable alternative for conducting in vivo experiments in human beings, especially at the preclinical study phase of monoclonal anti-D antibodies.